Proof-of-concept for a miniaturized shake-flask biopharmaceutical solubility determination by sonic mixing

Veseli, Ardita (author), Kristl, Albin (author), Žakelj, Simon (author)

The solvent volume must be very small to obtain biopharmaceutically relevant drug solubility data with low consumption of the solid sample which is often in low supply during early drug development. However, the adequate and repeatable mixing of a small volume can be challenging. We therefore developed a straightforward technique based on the shake-flask method which employed only sonication for mixing a very small amount of drug in an aqueous solvent at a stable pH and temperature. To test the technique, the solubilities of the model compounds carvedilol, digoxin, propranolol, theophylline, and verapamil were determined. The determined solubility values agreed well with the conventional shake-flask solubility data obtained in our laboratory and previously published literature data. The time necessary for the measurements (24 h), was shown to be similar to the conventional shake-flask method even for the low solubility drugs digoxin and carvedilol. The solubility % pH dependence can be established very well as shown with verapamil and propranolol and confirmed with a pH in-dependent solubility of theophylline.

• Language: English
• Keywords: pharmacokinetics, physiologically based pharmacokinetic (PBPK) modeling gastro plus modeling, clinical trial simulation(s), bioequivalence, biopharmaceutics classification system (BCS), virtual bioequivalence (VBE)
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: Str. 626-631
• Numbering: Vol. 75, no. 12
• PID: 20.500.12556/RUL-141963
• UDC: 544.351.3:615
• ISSN on article: 0031-7144
• DOI: 10.1691/ph.2020.0063
• COBISS.SI-ID: 40934147
• Publication date in RUL: 13.10.2022

Record is a part of a journal

• Title: Pharmazie
• Shortened title: Pharmazie
• Publisher: Verlag Volk und Gesundheit
• ISSN: 0031-7144
• COBISS.SI-ID: 1720079

Secondary language

• Language: Slovenian
• Keywords: biofarmacija, farmakokinetika, modeliraje, simulacije kliničnih poskusov, bioekvivalenca

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0189-2018
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih